Huntingtons's Disease (HD) is an autosomal dominant neurological disorder caused by the inheritance of a CAG repeat greater than 36 in length in exon 1 of a gene of unknown function, huntingtin [1,2]. There is no known cure for this lethal neurological disorder, however, progress has been made in identifying candidate processes and in the development high-throughput screens to identify potential therapeutics. The broad long term goal of this project is to help design tools to aid in therapeutic discovery for HD. An important tool in testing the efficacy of therapeutic candidates is an animal model that accurately replicates the molecular pathology of HD. Knock-in mouse models of HD currently have the greatest potential for accurately mimicking the disease, but have a phenotype so mild that experimental testing of therapeutics in these models would presently be difficult. The goals of this proposal are to 1) determine whether increasing the repeat length of a knock-in HD mouse model will overcome this difficulty, 2) to provide the field with a panel of HD knock-ins with different repeat lengths (100,150, 200 and 250 CAGs) congenic to two different inbred mouse lines (C57Bl/6 and CBA), 3) to provide reliable baseline [phenotype information to researchers interested in testing potential therapeutics. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS059647-02
Application #
7422316
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Sutherland, Margaret L
Project Start
2007-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2010-06-30
Support Year
2
Fiscal Year
2008
Total Cost
$158,594
Indirect Cost
Name
University of Alabama Birmingham
Department
Biochemistry
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Heng, Mary Y; Detloff, Peter J; Paulson, Henry L et al. (2010) Early alterations of autophagy in Huntington disease-like mice. Autophagy 6:1206-8
Heng, Mary Y; Duong, Duy K; Albin, Roger L et al. (2010) Early autophagic response in a novel knock-in model of Huntington disease. Hum Mol Genet 19:3702-20
Perry, Giselle M; Tallaksen-Greene, Sara; Kumar, Ashish et al. (2010) Mitochondrial calcium uptake capacity as a therapeutic target in the R6/2 mouse model of Huntington's disease. Hum Mol Genet 19:3354-71